Posted in Pharmacology

First-pass metabolism, also known as the first-pass effect, is a phenomenon that occurs as medication is metabolized by the body and made less effective. In this article, we’ll review the first-pass effect and its implications for your nursing practice. You can review first-pass metabolism on-the-go in episode 368 of the Straight A Nursing podcast.

Bioavailability

To understand the first-pass effect, it’s important to first understand the concept of bioavailability. Bioavailability refers to how extensively and quickly the active form of a drug reaches systemic circulation. It is measured in percentages which represent how much of the drug is ultimately available to exert its effects on its site of action. Medications given IV have 100% bioavailability, whereas medications given orally do not, thanks to the first-pass effect. 

How PO medications are metabolized

Now let’s look at what happens when a medication is administered PO. When a medication is swallowed, it enters the stomach and then the intestine. From there it passes through the intestinal wall and enters portal circulation. Portal circulation refers to a network of capillaries and the portal vein, which drain the majority of nutrient-rich blood from the digestive tract and empty it into the liver. And since the liver is a major organ of drug metabolism, in many cases, a portion of the drug is essentially destroyed here. Any medication that remains then travels to the heart where it is pumped out into systemic circulation. This is why medications administered PO undergo the first-pass effect. In short, they are going to the liver and being metabolized before they enter systemic circulation. However, it is important to note that this effect is variable and not all medications are affected by first-pass metabolism in the same way.

Some medications have what is called a “heavy first-pass effect.” This means that when taken by mouth, very little of the actual drug enters systemic circulation. This is why you will see much higher PO doses of some medications and also why there are so many alternative routes available (IV, transdermal, sublingual, etc…).

You will also notice that with many drugs, the IV dose and PO dose are the same. A great example is the medication pantoprazole, which undergoes very little first-pass metabolism and has a bioavailability of about 77%. Another medication with equivalent PO and IV dosing is levothyroxine. Studies show that levothyroxine does not undergo significant first-pass metabolism and has an oral bioavailability of up to 80% when given on an empty stomach.

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What does this mean for you as a nurse?

Essentially, understanding this concept enables you to understand the proper dosing of medications, especially those that experience significant first-pass metabolism (ex: morphine or diazepam.) It also helps you understand when a medication is expected to have its intended effect. A medication that reaches peak concentration more quickly is going to have a faster onset of action than a medication that reaches peak concentration more slowly.

A pediatric patient weighing 19 kg is scheduled for surgery and due to receive midazolam as a sedative prior to the procedure. The MD orders 0.5 mg/kg PO midazolam (9.5 mg). When you remind her the patient is NPO, she thanks you profusely and changes the order to IV. Do you expect the IV dose to be higher than the PO dose or lower?

Let’s look at a few different medications to drive the concept of first pass metabolism home.

Nitroglycerin – A medication that undergoes significant first-pass metabolism is nitroglycerin. Nitrates are almost entirely metabolized by the liver, which is why they are not taken PO. Nitroglycerin is administered via alternate routes such as sublingual, transdermal, and intravenously. 

Morphine – A common PO dose of morphine for an adult patient is 30 mg. However, a common IV dose is in the range of 2 to 10 mg.

Propranolol – Propranolol is a beta blocker that undergoes significant first-pass metabolism. A common PO dose in an adult is 80 to 320 mg per day in two to four divided doses. So, each dose could be as high 80 mg (if 320 mg is divided into four doses). In contrast, an IV dose of propranolol is 1 to 3 mg. Studies show it has a bioavailability of 15 to 23 percent.

Buprenorphine – This medication, which is used to treat severe chronic pain and opioid disorder, has a heavy first-pass effect with a PO bioavailability of just 10 to 15 percent. This is why it is administered through alternate routes such as SubQ, buccal, and sublingual. Studies show that the bioavailability of sublingual buprenorphine is 60 to 70 percent.

I hope this breakdown of first-pass metabolism has helped you understand this foundation pharmacology concept. After all, pharm can be a tough subject for a lot of students. That’s why I created Fast Pharmacology an audio-based program where I teach foundation pharmacology concepts and drug classes in five minutes or less! Stop struggling in pharm and start understanding it. Click here to get access!

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References:

Corbo, M., Liu, J.-C., & Chien, Y. W. (1990). Bioavailability of propranolol following oral and transdermal administration in rabbits. Journal of Pharmaceutical Sciences, 79(7), 584–587. https://doi.org/10.1002/jps.2600790707

Dean, L., & McEntyre, J. (2004, July 7). Figure 3, The portal circulation [Text]. https://www.ncbi.nlm.nih.gov/books/NBK1671/figure/A203/

Ernstmeyer, K., & Christman, E. (2023). Chapter 1 Pharmacokinetics & Pharmacodynamics. In Nursing Pharmacology [Internet]. 2nd edition. Chippewa Valley Technical College. https://www.ncbi.nlm.nih.gov/books/NBK595006/

FDA. (n.d.). Protonix (pantoprazole sodium). FDA.gov. https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/20987lbl.pdf

Herman, T. F., & Santos, C. (2024). First-Pass Effect. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK551679/

Le, J. (2022, June). Drug Bioavailability – Clinical Pharmacology. Merck Manual Professional Edition. https://www.merckmanuals.com/professional/clinical-pharmacology/pharmacokinetics/drug-bioavailability

Lilja, J. J., Laitinen, K., & Neuvonen, P. J. (2005). Effects of grapefruit juice on the absorption of levothyroxine. British Journal of Clinical Pharmacology, 60(3), 337–341. https://doi.org/10.1111/j.1365-2125.2005.02433.x

PhysioPathoPharmaco. (2019, February 21). Bioavailability and First Pass Metabolism [Video recording]. https://www.youtube.com/watch?app=desktop&v=BQQns7RAUzA

ScienceDirect. (n.d.). Buprenorphine. ScienceDirect. https://www.sciencedirect.com/topics/medicine-and-dentistry/buprenorphine

Vallerand, A. H., & et al. (2024). Midazolam (Nayzilam, Seizalam). In Davis’s Drug Guide (19th ed.). F.A. Davis Company. https://www.drugguide.com/ddo/view/Davis-Drug-Guide/51501/all/midazolam?refer=true

Vallerand, A. H., & et al. (2024). Propranolol (Hemangeol, Inderal). In Davis’s Drug Guide (19th ed.). F.A. Davis Company. https://www.drugguide.com/ddo/view/Davis-Drug-Guide/51642/all/propranolol?refer=true

Last Updated on October 15, 2024 by Maureen Osuna, MSN, RN